Intergenerational Transmission of Risk for Depression

Grandchildren with both a depressed parent and depressed grandparent were at highest risk for MDD.

Epigenetic inheritance is known to play a role in the effects of nutrition and undernutrition on increased risk of cardiovascular disease, diabetes, and neonatal adiposity across generations. Epigenetic alterations that occur as a consequence of exposure to traumatic stress and that are then transmitted across generations to influence the development of neuropsychiatric symptoms in offspring have been documented in humans. For example, this concept may explain the higher prevalence of lifetime neuropsychiatric, stress-related illness such as posttraumatic stress disorder (PTSD) in offspring of Holocaust survivors compared to that in a control population.

Researchers affiliated with Columbia University, New York State Psychiatric Institute, and New York Presbyterian Hospital recently reported the higher prevalence of depressive symptoms in offspring of parents and grandparents who were diagnosed with major depressive disorder (MDD) compared to that in a control population.

“The increased risk of psychiatric disorders in the offspring of depressed parents is well known, [but] whether this risk is transmitted beyond 2 generations is less well known,” the investigators wrote in their study published in JAMA Psychiatry. Although the sample was relatively small (n=62 families), this is the first longitudinal retrospective cohort study to include direct interviews of family members across 3 generations (ie, offspring, parents, grandparents) and to evaluate the risk for depression beyond 2 generations. Data were collected between 1982 (wave 1) and 2015 (wave 6).

In line with previously reported data, the biological children of depressed parents had 2-fold increased risk for MDD [hazard ratio (HR), 2.02; 95% CI, 1.08-3.79; P=0.03], substance dependence (HR, 2.96; 95% CI, 1.24-7.08; P=0.01), and suicidal ideation or gesture (HR), 2.44; 95% CI, 1.28-4.66; P=0.007), compared to those of non-depressed parents. No evidence of increased risk across generations was found for bipolar disorder or schizophrenia.

When all 3 generations were examined, data show that more than 70% of grandchildren with both a depressed parent and depressed grandparent had at least one psychiatric disorder, and were at highest risk for MDD. “Only the association between parental and grandchild depression is moderated by grandparent major depression,” and “this finding suggests the value of screening for MDD beyond 2 generations,” the authors concluded.